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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
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RHEB activates MTOR. 10 / 339
2 | 3 107 217
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"Indeed, we have shown, as a proof of principle, that knocking down TSC2 or overexpressing RHEB enhances mTOR activity in KO cells."
sparser
"Rheb activation of mTOR is more dependent on farnesylation than on postprenylation CAAX processing."
sparser
"The TSC complex naturally inhibits a protein termed Rheb (Ras homolog enriched in brain) that activates mTOR [ xref ]."
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"This explains why overexpressed Rheb activates mTOR in the absence of amino acids; presumably the Rheb-mTOR interaction is driven by mass action in this case, and no longer requires the amino acid stimulated movement of mTOR to late endosomes."
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"Rheb has been shown to exclusively activate the mTOR pathway without affecting other signaling pathways."
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"Akt mediated phosphorylation can downregulate tuberin 's GTPase activating potential toward Rheb, which modulates mTOR complex 1 through FKBP38 by directly binding to mTOR [XREF_BIBR]."
sparser
"Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [ xref ], though this remains controversial [ xref ]."
sparser
"Full-length TSC2 protein interacts with TSC1 to inhibit the activation of mTOR by Rheb."
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"Rheb is the upstream activator of mTOR."
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"When free of TSC1/2, RHEB activates mTOR within a rapamycin sensitive protein complex called mTORC1."
GTP-bound active RHEB activates MTOR. 10 / 21
11 10 |
bel
"Akt then phosphorylates several substrates, one of which is the tuberous sclerosis complex (TSC1/2), a GTPase activating protein complex that suppresses Rheb, a GTPase that contributes directly to the activation of mTOR"
bel
"The TOR complex 1 is a direct target of Rheb-GTP, whose binding enables activation of the TOR kinase"
bel
"Genetic support for a linear Akt1-mTOR-p70S6K pathway has recently come from reports demonstrating that the tuberous sclerosis complex 1 and 2 proteins (Tsc1 and Tsc2) can inhibit mTOR (Fig. 1). Akt1 phosphorylates Tsc2, thereby activating mTOR at least in part by disrupting the Tsc1-Tsc2 complex [54]."
bel
"Involvement of Rheb in the insulin TOR S6K signaling pathway was further investigated in mammalian cells. Transient transfection of Rheb1 or Rheb2 in HEK293 cells results in the increase of the phosphorylation of ribosomal S6 kinase (S6K) 25,30-33. Increase of the phosphorylation of S6 as well as 4E-BP1 was observed 30,31,33. In contrast, Rheb did not stimulate Akt phosphorylation 30,33]. The increase of S6K activity by the transient expression of Rheb was inhibited by the addition of rapamycin but not by wortmannin, an inhibitor of PI3K This led to the activation of S6K as detected by its phosphorylation. However, expression of dominant negative Rheb mutant, Rheb1D60K, blocked serum-inducted activation of S6K The overall picture of the involvement of Rheb in the insulin mTOR S6K signaling pathway is shown in Fig. 3. During serum activation of this signaling pathway, insulin or IGF1 is received by their respective receptors at the cell surface. This results in the activation of PI3K, which then phosphorylates Akt. The activated Akt phosphorylates Tsc2 and inhibits the ability of Tsc1 Tsc2 to negatively regulate mTOR. The inhibition of Tsc1 Tsc2 leads to the activation of Rheb, which then causes activation of mTOR. At least two downstream events, activation of p70S6K and phosphorylation of S6, as well as phosphorylation of 4E BP1 contribute to the increase in protein synthesis and progression of cell cycle49."
bel
"Genetic support for a linear Akt1-mTOR-p70S6K pathway has recently come from reports demonstrating that the tuberous sclerosis complex 1 and 2 proteins (Tsc1 and Tsc2) can inhibit mTOR (Fig. 1). Akt1 phosphorylates Tsc2, thereby activating mTOR at least in part by disrupting the Tsc1-Tsc2 complex [54]."
bel
"Rheb, in its GTP-bound state, can activate mTOR."
bel
"##full text## H9 cells expressing a GFP-tagged Rheb protein (a GTPase upstream of mTOR) moderately increased phosphorylated S6K1 levels over those expressing GFP alone (Fig. 3B)."
bel
"Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway"
bel
"Although the mechanism through which the TSC1-TSC2 complex represses mTOR signalling is incompletely defined, recent studies (Garami et al. 2003; Zhang et al. 2003) have suggested that, in part, TSC2 may act through the small GTPase ras homologue enriched in brain (Rheb) in regulating mTOR. Here, TSC2 is a GTPase-activating protein for Rheb that normally represses Rheb function (Garami et al. 2003; Zhang et al. 2003). How Rheb modulates mTOR-dependent signalling is unknown."
bel
"Rheb, in its GTP-bound state, can activate mTOR."
RHEB bound to GTP activates MTOR. 7 / 7
| 7
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"The main conclusion of our study is that RGS10 suppression causes an increase in activated, GTP bound Rheb and results in mTOR pathway activation among ovarian cancer cells."
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"PI3K and Akt signaling suppresses the activity of the Rheb GTPase activating complex (TSC1 and TSC2) and thereby increases the level of GTP bound Rheb, which in turn induces mTOR signaling [XREF_BIBR]."
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"GTP bound Rheb activates the mTOR kinase activity."
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"Therefore, the sequestration of TSC2 with 14-3-3 increases the relative amount of GTP bound Rheb and this activates mTOR in muscle cells XREF_BIBR."
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"Moreover, activation of Akt has been reported to inactivate the TSC1/2 complex, leading to increased active GTP bound Rheb, which activates mTOR XREF_BIBR."
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"In this case, GTP bound RHEB activates mTOR."
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"Rheb when associated with GTP stimulates mTOR activity [XREF_BIBR]."
RHEB bound to MTOR activates MTOR. 2 / 2
| 2
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"There is some evidence indicating that Rheb, a small guanosine triphosphate (GTP)-binding protein, interacts with mTOR and activates the enzymatic activity of mTOR by binding the Rheb-GTP to mTOR directly."
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"Rheb interacts directly with mTOR and activates mTOR kinase, whereas Rabin8 interacts with Rheb and inhibits the phosphorylation of Ser235 and Ser236 in small ribosomal subunit protein S6."
RHEB bound to FKBP8 activates MTOR. 1 / 1
| 1
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"In this model, GTP bound Rheb binds to FKBP38 and induces the release and activation of mTOR."
RHEB activates mutated MTOR. 1 / 1
| 1
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"To examine the role of mTOR in metformin 's action on tau phosphorylation, we inhibited its activity with rapamycin, or activated it by overexpressing a constitutive active mutant of the mTOR activator Rheb (S16H-Rheb) [XREF_BIBR]."
Active RHEB activates MTOR. 1 / 1
| 1
trips
"Expression of a constitutively active Rheb enhanced mTOR activity and increased the fiber size in VCP-IBM mouse skeletal muscle."